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Study of Lenalidomide to Evaluate Safety and Effectiveness in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

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ClinicalTrials.gov Identifier: NCT01197560
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : August 20, 2014
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diffuse Large B-cell Lymphoma
Interventions Drug: Lenalidomide
Drug: Gemcitabine
Drug: Oxaliplatin
Drug: Rituximab
Drug: Etoposide
Enrollment 111
Recruitment Details Screening and enrollment occurred at 43 sites, including 10 in the United States, 9 in France, 7 in the United Kingdom; 4 in Spain, 4 in Italy, 3 each in Austria and Australia, 2 in the Czech Republic, and 1 in Sweden.
Pre-assignment Details Participants were stratified into Germinal center B-cell (GCB) or non-GCB subtypes and randomized 1:1 to receive lenalidomide or investigator’s choice treatment (one of the single-agent reference therapies [gemcitabine, rituximab, etoposide, or oxaliplatin)
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Period Title: Overall Study
Started 54 [1] 57 [1]
Received ≥ One Dose Study Drug 54 55
Lenalidomide Crossover 0 29
Discontinued Treatment After ≥ 6 Cycles 14 0
Completed [2] 0 4
Not Completed 54 53
Reason Not Completed
Adverse Event             6             8
Death             3             5
Withdrawal by Subject             1             1
Disease progression             40             35
Miscellaneous             4             3
Missing             0             1
[1]
This is the intent to treat population
[2]
Completed indicates the participates who completed core treatment.
Arm/Group Title Lenalidomide Investigators Choice (IC) Total
Hide Arm/Group Description Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles Total of all reporting groups
Overall Number of Baseline Participants 51 51 102
Hide Baseline Analysis Population Description
Modified Intent to Treat (mITT) = all study participants randomized with a diffuse large B-cell lymphoma (DLBCL) diagnosis and germinal center B-cell (GCB)/non-germinal center B (non-GCB) subtype confirmed by central pathology, and who received at least one dose of study drug (lenalidomide or Investigator’s choice). Nine participants were excluded.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 51 participants 102 participants
64.7  (13.43) 62.8  (13.94) 63.75  (13.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
Female
21
  41.2%
20
  39.2%
41
  40.2%
Male
30
  58.8%
31
  60.8%
61
  59.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
Asian
1
   2.0%
1
   2.0%
2
   2.0%
Black/African American
0
   0.0%
1
   2.0%
1
   1.0%
White
38
  74.5%
36
  70.6%
74
  72.5%
Missing
9
  17.6%
11
  21.6%
20
  19.6%
Other (Unspecified)
3
   5.9%
2
   3.9%
5
   4.9%
Eastern Cooperative Oncology Performance Status (ECOG)]   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
0 = (Fully Active)
18
  35.3%
15
  29.4%
33
  32.4%
1 (Restrictive but Ambulatory)
24
  47.1%
28
  54.9%
52
  51.0%
2 (Ambulatory but Unable to Work)
7
  13.7%
8
  15.7%
15
  14.7%
3 (Limited Self-Care)
0
   0.0%
0
   0.0%
0
   0.0%
4 (Completely Disabled)
1
   2.0%
0
   0.0%
1
   1.0%
Missing
1
   2.0%
0
   0.0%
1
   1.0%
[1]
Measure Description: ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)
Creatinine Clearance (CrCl)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
≥ 60 mL/min
32
  62.7%
43
  84.3%
75
  73.5%
≥ 30 but < 60 mL/min
18
  35.3%
7
  13.7%
25
  24.5%
Missing
1
   2.0%
1
   2.0%
2
   2.0%
[1]
Measure Description: Creatinine is a waste product from the normal breakdown of muscle tissue. As creatinine is produced, it's filtered through the kidneys and excreted in urine. Doctors measure the blood creatinine level as a test of kidney function. Participants with a CrCl (as calculated by the Cockcroft-Gault formula, utilizing actual body weight or ideal body weight, whichever was less) of ≥ 60 mL/min received a starting dose of 25 mg lenalidomide once daily. Participants with moderate renal insufficiency (ie, CrCl ≥ 30 mL/min but < 60 mL/min) received a starting dose of 10 mg lenalidomide once daily.
Disease Stage of DLBCL at Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
IA
1
   2.0%
3
   5.9%
4
   3.9%
IB
1
   2.0%
0
   0.0%
1
   1.0%
IIA
8
  15.7%
7
  13.7%
15
  14.7%
IIB
3
   5.9%
1
   2.0%
4
   3.9%
IIIA
13
  25.5%
13
  25.5%
26
  25.5%
IIIB
2
   3.9%
4
   7.8%
6
   5.9%
IVA
17
  33.3%
14
  27.5%
31
  30.4%
IVB
6
  11.8%
9
  17.6%
15
  14.7%
[1]
Measure Description: The criteria for Clinical Stage (Ann Arbor staging) are as below: I: involvement of a single nodal region. II: involvement of 2 or more lymph node regions on the same side of the diaphragm. III: involvement of lymph node regions on both sides of the diaphragm. IV: disseminated involvement of 1 or more extra-lymphatic sites with or without associated lymph node involvement. A or B: the absence of constitutional (B-type) symptoms is denoted by adding an "A" to the stage; the presence is denoted by adding a "B" to the stage.
Diffuse Large B-Cell Lymphoma (DLBCL) Subtypes - Germinal Center B-Cell (GCB) and non-GCB   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
Germinal Center B-Cell Type
23
  45.1%
25
  49.0%
48
  47.1%
Non-Germinal Center B-Cell Type
28
  54.9%
26
  51.0%
54
  52.9%
[1]
Measure Description: DLBCL is comprised of different pathophysiological subtypes that influence patient prognosis and response to treatment. Based on immunohistochemistry (IHC), DLBCL can be classified into germinal center B-cell (GCB) and non-GCB subtypes. Patients with non-GCB have a worse prognosis compared with the GCB subtype
[2]
Measure Analysis Population Description: The Modified Intent to Treat (mITT ) population was defined as all participants randomized who had a DLBCL diagnosis and either Germinal Center B-cell subtype or non-GCB subtype confirmed by central pathology, and who received at least one dose of study drug (lenalidomide or investigator's choice).
1.Primary Outcome
Title Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC)
Hide Description An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease.
Time Frame From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Intent to Treat (mITT) population was defined as all participants randomized who had a diffuse large B-cell lymphoma (DLBCL) diagnosis and either germinal center B-cell subtype (GCB) or non-GCB subtype confirmed by central pathology, and who received at least one dose of study drug (lenalidomide or investigator’s choice).
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
ORR for All Participants Number Analyzed 51 participants 51 participants
27.5
(15.9 to 41.7)
11.8
(4.4 to 23.9)
GCB Subtype Number Analyzed 23 participants 25 participants
26.1
(10.2 to 48.4)
12.0
(2.5 to 31.2)
Non-GCB Number Analyzed 28 participants 26 participants
28.6
(13.2 to 48.7)
11.5
(2.4 to 30.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (IC)
Comments Pertains to all participants; row 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Investigators Choice (IC)
Comments Pertains to GCB Subtype; row 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.279
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Investigators Choice (IC)
Comments Pertains to non-GCB Sub-type; row 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.179
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Primary Outcome
Title Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase
Hide Description Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
29.4
(17.5 to 43.8)
13.7
(5.7 to 26.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (IC)
Comments Pertains to all participants
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment
Hide Description

A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.

A serious adverse event (SAE) is any:

  • Death;
  • Life-threatening event;
  • Any inpatient hospitalization or prolongation of existing hospitalization;
  • Persistent or significant disability or incapacity;
  • Congenital anomaly or birth defect;
  • Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death
Time Frame From first dose of study drug to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least one dose of lenalidomide or IC regimen.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 54 55
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
54
 100.0%
55
 100.0%
Any Treatment Related TEAE
49
  90.7%
45
  81.8%
Any TEAE Grade ≥ 3
43
  79.6%
53
  96.4%
Any TEAE Grade ≥ 4
29
  53.7%
36
  65.5%
Any TEAE Grade 5
9
  16.7%
18
  32.7%
Any TEAE Grade 3 or 4
42
  77.8%
52
  94.5%
Any Treatment Related TEAE Grade ≥ 3
30
  55.6%
39
  70.9%
Any Treatment Related TEAEs Grade ≥ 4
15
  27.8%
21
  38.2%
Any Treatment Related TEAE Grade 5
0
   0.0%
2
   3.6%
Any Treatment Related TEAE Grade 3 or 4
30
  55.6%
39
  70.9%
Any Serious Adverse Events (SAEs)
31
  57.4%
42
  76.4%
Any Treated Related SAEs
14
  25.9%
21
  38.2%
Any AE leading to stopping of study drug
11
  20.4%
17
  30.9%
Any drug related AE leading to halt of study drug
5
   9.3%
4
   7.3%
Any AE leading to dose interruption/reduct
32
  59.3%
34
  61.8%
Any drug related AE leading to interruption/reduct
27
  50.0%
30
  54.5%
4.Secondary Outcome
Title Stage 2: Overall Response Rate (ORR)
Hide Description ORR is defined as: Complete Response + Complete Response unconfirmed + Partial Response based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
ORR not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Stage 2: Duration of Response (DoR)
Hide Description Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
DoR not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Stage 2: Overall Survival (OS)
Hide Description Overall survival was defined as time from randomization until death of any cause.
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
OS not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Stage 2: Duration of Complete Response
Hide Description Length of time of complete response (Complete Response + Complete Response unconfirmed) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Duration of CR was not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Stage 2: Overall Response Rate for With a Duration of Response Lasting ≥ 16 Weeks
Hide Description Complete Response + Complete Response unconfirmed + Partial Response for participants with a duration of response lasting ≥ 16 weeks based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Overall Response Rate for with a Duration of Response Lasting ≥ 16 weeks was not analyzed: the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Stage 2: Time to Progression
Hide Description Length of time until disease progression occurs
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Time to progression was not analyzed; the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Stage 2: Health Related Quality of Life Questionnaires
Hide Description Quality of Life based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EQ-5D assessments
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life Instruments were not analyzed; the Stage 1 results as assessed by the IRAC, demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Other Pre-specified Outcome
Title Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Hide Description Durable overall response rate was defined as the percentage of participants who maintained a response for at least 16 weeks after initial response.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 51 51
Median (95% Confidence Interval)
Unit of Measure: percentage of participants
23.5
(12.8 to 37.5)
9.8
(3.3 to 21.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (Control Arm)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
12.Other Pre-specified Outcome
Title Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Hide Description A complete response was defined as participants with a complete response (CR), or unconfirmed complete response (CRu) based on IWG 1999 Response Criteria for NHL as assessed by the investigator. A CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRu) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.7
(5.7 to 26.3)
3.9
(0.5 to 13.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (IC)
Comments Pertains to all participants; row 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
13.Other Pre-specified Outcome
Title Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Hide Description Duration of overall response was calculated as the time of initial response (CR+CRu+PR) until documented disease progression determinted by computerized scan CT scan or MRI or death due to lymphoma, whichever occurred earlier, for participants who responded.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
For DoR, the population included participants who had an overall response.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 15 7
Median (95% Confidence Interval)
Unit of Measure: Weeks
64.7
(29.1 to 141.6)
63.1
(15.3 to 79.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (Control Arm)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.529
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
14.Other Pre-specified Outcome
Title Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Hide Description Duration of complete response was defined as the time from the first documented complete response (CR + CRu) until the first disease progression or death for participants who had a CR.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
For DoCR, the population included participants who had a CR.
Arm/Group Title Lenalidomide Investigators Choice (Control Arm)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Participants with documented progressive disease had the option to receive crossover lenalidomide at the same dosage as participants randomized to lenalidomide.
Overall Number of Participants Analyzed 7 2
Median (95% Confidence Interval)
Unit of Measure: Weeks
66.4 [1] 
(22.1 to NA)
179.3
(63.1 to 295.4)
[1]
No estimable due to that the estimated upper 97.5% survival curve does not reach 50%.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (Control Arm)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.972
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
15.Other Pre-specified Outcome
Title Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase
Hide Description Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 51 51
Median (95% Confidence Interval)
Unit of Measure: Weeks
9.6
(7.6 to 17.1)
7.1
(6.0 to 8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (IC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
16.Other Pre-specified Outcome
Title Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase
Hide Description Overall survival was defined as time from randomization until death of any cause.
Time Frame From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
mITT was defined as all participants randomized who had a DLBCL diagnosis confirmed by central pathology, had either GCB or non-GCB subtype and received at least one dose of study drug or investigators choice regimen.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 51 51
Median (95% Confidence Interval)
Unit of Measure: Weeks
31.0
(16.6 to 43.7)
24.6
(12.7 to 34.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide, Investigators Choice (IC)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.211
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
17.Other Pre-specified Outcome
Title Stage 2: Progression-Free Survival
Hide Description Number of participants who survive without progressing based on the International Working Group Response Criteria [IWG].
Time Frame Approximately 3.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
PFS not analyzed; the Stage 1 results as assessed by the independent response adjudication committee (IRAC), demonstrated that neither subtype met the pre-specified requirement to be further studied in Stage 2. Study terminated after Stage 1 completed and before Stage 2 started.
Arm/Group Title Lenalidomide Investigators Choice (IC)
Hide Arm/Group Description:
Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal. Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only) Etoposide doses: 100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From first dose of study drug to the final data cut-off date of 18 May 2018; the median study duration of 27.0 and 19.7 weeks, respectively.
Adverse Event Reporting Description The AEs were based on the overall treatment phase that includes both core treatment phase and crossover phase. Two participants in the investigator choice arm elected to discontinue before cycle 1; secondary primary malignancies were monitored up to final database lock of 18 May 2018
 
Arm/Group Title Lenalidomide Investigator's Choice
Hide Arm/Group Description Participants received lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may have been increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal. Investigator's Choice
All-Cause Mortality
Lenalidomide Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%)
Total   48/54 (88.89%)   51/55 (92.73%) 
Show Serious Adverse Events Hide Serious Adverse Events
Lenalidomide Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%)
Total   31/54 (57.41%)   42/55 (76.36%) 
Blood and lymphatic system disorders     
ANAEMIA  1  4/54 (7.41%)  3/55 (5.45%) 
FEBRILE BONE MARROW APLASIA  1  0/54 (0.00%)  1/55 (1.82%) 
FEBRILE NEUTROPENIA  1  4/54 (7.41%)  2/55 (3.64%) 
LYMPH NODE PAIN  1  0/54 (0.00%)  1/55 (1.82%) 
THROMBOCYTOPENIA  1  1/54 (1.85%)  3/55 (5.45%) 
Cardiac disorders     
ATRIAL FIBRILLATION  1  1/54 (1.85%)  0/55 (0.00%) 
CARDIAC ARREST  1  0/54 (0.00%)  1/55 (1.82%) 
CARDIAC FAILURE CONGESTIVE  1  1/54 (1.85%)  0/55 (0.00%) 
CARDIO-RESPIRATORY ARREST  1  0/54 (0.00%)  1/55 (1.82%) 
MYOCARDIAL INFARCTION  1  0/54 (0.00%)  1/55 (1.82%) 
SUPRAVENTRICULAR TACHYCARDIA  1  1/54 (1.85%)  0/55 (0.00%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  0/54 (0.00%)  1/55 (1.82%) 
COLITIS ULCERATIVE  1  1/54 (1.85%)  0/55 (0.00%) 
DIARRHOEA  1  0/54 (0.00%)  1/55 (1.82%) 
DUODENAL OBSTRUCTION  1  1/54 (1.85%)  0/55 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE  1  1/54 (1.85%)  0/55 (0.00%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  1/54 (1.85%)  0/55 (0.00%) 
ILEUS  1  1/54 (1.85%)  1/55 (1.82%) 
LARGE INTESTINE PERFORATION  1  1/54 (1.85%)  0/55 (0.00%) 
LOWER GASTROINTESTINAL HAEMORRHAGE  1  1/54 (1.85%)  0/55 (0.00%) 
NAUSEA  1  0/54 (0.00%)  1/55 (1.82%) 
SMALL INTESTINAL OBSTRUCTION  1  1/54 (1.85%)  0/55 (0.00%) 
VOMITING  1  0/54 (0.00%)  3/55 (5.45%) 
General disorders     
ASTHENIA  1  0/54 (0.00%)  2/55 (3.64%) 
DEATH  1  1/54 (1.85%)  0/55 (0.00%) 
FATIGUE  1  0/54 (0.00%)  1/55 (1.82%) 
GENERAL PHYSICAL HEALTH DETERIORATION  1  1/54 (1.85%)  2/55 (3.64%) 
MULTIPLE ORGAN DYSFUNCTION SYNDROME  1  0/54 (0.00%)  1/55 (1.82%) 
NON-CARDIAC CHEST PAIN  1  0/54 (0.00%)  1/55 (1.82%) 
PERFORMANCE STATUS DECREASED  1  0/54 (0.00%)  1/55 (1.82%) 
PYREXIA  1  2/54 (3.70%)  2/55 (3.64%) 
Hepatobiliary disorders     
BILE DUCT OBSTRUCTION  1  1/54 (1.85%)  0/55 (0.00%) 
Infections and infestations     
CELLULITIS  1  0/54 (0.00%)  4/55 (7.27%) 
DIARRHOEA INFECTIOUS  1  0/54 (0.00%)  1/55 (1.82%) 
GASTROENTERITIS  1  1/54 (1.85%)  1/55 (1.82%) 
INFECTION  1  1/54 (1.85%)  1/55 (1.82%) 
LOWER RESPIRATORY TRACT INFECTION  1  1/54 (1.85%)  0/55 (0.00%) 
LUNG ABSCESS  1  0/54 (0.00%)  1/55 (1.82%) 
LUNG INFECTION  1  1/54 (1.85%)  1/55 (1.82%) 
LYMPH NODE ABSCESS  1  0/54 (0.00%)  1/55 (1.82%) 
NEUTROPENIC SEPSIS  1  0/54 (0.00%)  1/55 (1.82%) 
PNEUMONIA  1  3/54 (5.56%)  3/55 (5.45%) 
RESPIRATORY TRACT INFECTION  1  1/54 (1.85%)  0/55 (0.00%) 
SEPSIS  1  1/54 (1.85%)  2/55 (3.64%) 
SEPTIC SHOCK  1  1/54 (1.85%)  2/55 (3.64%) 
STAPHYLOCOCCAL SEPSIS  1  0/54 (0.00%)  1/55 (1.82%) 
SUBCUTANEOUS ABSCESS  1  0/54 (0.00%)  1/55 (1.82%) 
URINARY TRACT INFECTION  1  2/54 (3.70%)  0/55 (0.00%) 
WOUND INFECTION  1  0/54 (0.00%)  1/55 (1.82%) 
Injury, poisoning and procedural complications     
FALL  1  0/54 (0.00%)  1/55 (1.82%) 
Investigations     
BLOOD CREATININE INCREASED  1  0/54 (0.00%)  1/55 (1.82%) 
NEUTROPHIL COUNT DECREASED  1  1/54 (1.85%)  0/55 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION  1  1/54 (1.85%)  1/55 (1.82%) 
HYPERCALCAEMIA  1  1/54 (1.85%)  3/55 (5.45%) 
TUMOUR LYSIS SYNDROME  1  1/54 (1.85%)  1/55 (1.82%) 
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  1/54 (1.85%)  0/55 (0.00%) 
JOINT SWELLING  1  1/54 (1.85%)  0/55 (0.00%) 
PAIN IN EXTREMITY  1  0/54 (0.00%)  2/55 (3.64%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
BASAL CELL CARCINOMA  1  1/54 (1.85%)  1/55 (1.82%) 
DIFFUSE LARGE B-CELL LYMPHOMA  1  4/54 (7.41%)  10/55 (18.18%) 
GASTROINTESTINAL TRACT ADENOMA  1  0/54 (0.00%)  1/55 (1.82%) 
LEUKAEMIA  1  1/54 (1.85%)  0/55 (0.00%) 
LYMPHOMA  1  0/54 (0.00%)  1/55 (1.82%) 
NON-HODGKIN'S LYMPHOMA  1  0/54 (0.00%)  1/55 (1.82%) 
RECTOSIGMOID CANCER METASTATIC  1  0/54 (0.00%)  1/55 (1.82%) 
TUMOUR FLARE  1  1/54 (1.85%)  0/55 (0.00%) 
Nervous system disorders     
CAUDA EQUINA SYNDROME  1  0/54 (0.00%)  1/55 (1.82%) 
CEREBROVASCULAR ACCIDENT  1  1/54 (1.85%)  0/55 (0.00%) 
DIZZINESS  1  0/54 (0.00%)  1/55 (1.82%) 
NERVE ROOT COMPRESSION  1  0/54 (0.00%)  1/55 (1.82%) 
SEIZURE  1  1/54 (1.85%)  1/55 (1.82%) 
Psychiatric disorders     
ANXIETY  1  0/54 (0.00%)  1/55 (1.82%) 
MENTAL STATUS CHANGES  1  0/54 (0.00%)  1/55 (1.82%) 
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  0/54 (0.00%)  1/55 (1.82%) 
HAEMATURIA  1  0/54 (0.00%)  2/55 (3.64%) 
HYDRONEPHROSIS  1  1/54 (1.85%)  0/55 (0.00%) 
NEPHROTIC SYNDROME  1  1/54 (1.85%)  0/55 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
ACUTE PULMONARY OEDEMA  1  0/54 (0.00%)  1/55 (1.82%) 
DYSPNOEA  1  2/54 (3.70%)  1/55 (1.82%) 
LARYNGEAL OBSTRUCTION  1  1/54 (1.85%)  0/55 (0.00%) 
OROPHARYNGEAL PAIN  1  1/54 (1.85%)  0/55 (0.00%) 
PHARYNGEAL INFLAMMATION  1  0/54 (0.00%)  1/55 (1.82%) 
PLEURAL EFFUSION  1  0/54 (0.00%)  1/55 (1.82%) 
PULMONARY EMBOLISM  1  2/54 (3.70%)  1/55 (1.82%) 
RESPIRATORY FAILURE  1  1/54 (1.85%)  1/55 (1.82%) 
STRIDOR  1  1/54 (1.85%)  0/55 (0.00%) 
Skin and subcutaneous tissue disorders     
FUNGATING WOUND  1  0/54 (0.00%)  1/55 (1.82%) 
Vascular disorders     
DEEP VEIN THROMBOSIS  1  0/54 (0.00%)  1/55 (1.82%) 
EMBOLISM  1  0/54 (0.00%)  1/55 (1.82%) 
HYPOTENSION  1  0/54 (0.00%)  1/55 (1.82%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lenalidomide Investigator's Choice
Affected / at Risk (%) Affected / at Risk (%)
Total   53/54 (98.15%)   52/55 (94.55%) 
Blood and lymphatic system disorders     
ANAEMIA  1  17/54 (31.48%)  31/55 (56.36%) 
LEUKOPENIA  1  3/54 (5.56%)  8/55 (14.55%) 
LYMPHOPENIA  1  1/54 (1.85%)  5/55 (9.09%) 
NEUTROPENIA  1  23/54 (42.59%)  18/55 (32.73%) 
THROMBOCYTOPENIA  1  13/54 (24.07%)  17/55 (30.91%) 
Cardiac disorders     
TACHYCARDIA  1  3/54 (5.56%)  1/55 (1.82%) 
Ear and labyrinth disorders     
HYPOACUSIS  1  0/54 (0.00%)  3/55 (5.45%) 
VERTIGO  1  3/54 (5.56%)  1/55 (1.82%) 
Gastrointestinal disorders     
ABDOMINAL DISTENSION  1  4/54 (7.41%)  1/55 (1.82%) 
ABDOMINAL PAIN  1  10/54 (18.52%)  12/55 (21.82%) 
CONSTIPATION  1  16/54 (29.63%)  16/55 (29.09%) 
DIARRHOEA  1  18/54 (33.33%)  16/55 (29.09%) 
DRY MOUTH  1  7/54 (12.96%)  3/55 (5.45%) 
DYSPEPSIA  1  3/54 (5.56%)  3/55 (5.45%) 
NAUSEA  1  10/54 (18.52%)  23/55 (41.82%) 
STOMATITIS  1  1/54 (1.85%)  5/55 (9.09%) 
VOMITING  1  9/54 (16.67%)  11/55 (20.00%) 
General disorders     
ASTHENIA  1  10/54 (18.52%)  13/55 (23.64%) 
CHILLS  1  4/54 (7.41%)  2/55 (3.64%) 
FATIGUE  1  19/54 (35.19%)  16/55 (29.09%) 
NON-CARDIAC CHEST PAIN  1  4/54 (7.41%)  1/55 (1.82%) 
OEDEMA PERIPHERAL  1  9/54 (16.67%)  10/55 (18.18%) 
PYREXIA  1  16/54 (29.63%)  18/55 (32.73%) 
Infections and infestations     
BRONCHITIS  1  6/54 (11.11%)  0/55 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION  1  3/54 (5.56%)  6/55 (10.91%) 
LUNG INFECTION  1  0/54 (0.00%)  3/55 (5.45%) 
NASOPHARYNGITIS  1  3/54 (5.56%)  1/55 (1.82%) 
PNEUMONIA  1  1/54 (1.85%)  3/55 (5.45%) 
RHINITIS  1  3/54 (5.56%)  4/55 (7.27%) 
UPPER RESPIRATORY TRACT INFECTION  1  5/54 (9.26%)  5/55 (9.09%) 
URINARY TRACT INFECTION  1  3/54 (5.56%)  4/55 (7.27%) 
Injury, poisoning and procedural complications     
DRUG PRESCRIBING ERROR  1  5/54 (9.26%)  1/55 (1.82%) 
Investigations     
ASPARTATE AMINOTRANSFERASE INCREASED  1  3/54 (5.56%)  1/55 (1.82%) 
BLOOD ALKALINE PHOSPHATASE INCREASED  1  0/54 (0.00%)  4/55 (7.27%) 
BLOOD CREATININE INCREASED  1  2/54 (3.70%)  4/55 (7.27%) 
BLOOD LACTATE DEHYDROGENASE INCREASED  1  0/54 (0.00%)  3/55 (5.45%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  0/54 (0.00%)  3/55 (5.45%) 
NEUTROPHIL COUNT DECREASED  1  0/54 (0.00%)  7/55 (12.73%) 
PLATELET COUNT DECREASED  1  0/54 (0.00%)  9/55 (16.36%) 
WHITE BLOOD CELL COUNT DECREASED  1  0/54 (0.00%)  5/55 (9.09%) 
Metabolism and nutrition disorders     
DECREASED APPETITE  1  8/54 (14.81%)  15/55 (27.27%) 
HYPERGLYCAEMIA  1  3/54 (5.56%)  6/55 (10.91%) 
HYPOCALCAEMIA  1  1/54 (1.85%)  3/55 (5.45%) 
HYPOKALAEMIA  1  6/54 (11.11%)  10/55 (18.18%) 
HYPOPHOSPHATAEMIA  1  1/54 (1.85%)  3/55 (5.45%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  7/54 (12.96%)  5/55 (9.09%) 
BACK PAIN  1  3/54 (5.56%)  8/55 (14.55%) 
MUSCLE SPASMS  1  4/54 (7.41%)  2/55 (3.64%) 
MUSCULAR WEAKNESS  1  3/54 (5.56%)  1/55 (1.82%) 
MUSCULOSKELETAL PAIN  1  3/54 (5.56%)  0/55 (0.00%) 
MYALGIA  1  4/54 (7.41%)  4/55 (7.27%) 
PAIN IN EXTREMITY  1  6/54 (11.11%)  5/55 (9.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
DIFFUSE LARGE B-CELL LYMPHOMA  1  3/54 (5.56%)  1/55 (1.82%) 
TUMOUR FLARE  1  5/54 (9.26%)  0/55 (0.00%) 
Nervous system disorders     
DIZZINESS  1  3/54 (5.56%)  5/55 (9.09%) 
DYSGEUSIA  1  2/54 (3.70%)  3/55 (5.45%) 
HEADACHE  1  3/54 (5.56%)  6/55 (10.91%) 
HYPOAESTHESIA  1  3/54 (5.56%)  1/55 (1.82%) 
LETHARGY  1  4/54 (7.41%)  1/55 (1.82%) 
PERIPHERAL SENSORY NEUROPATHY  1  2/54 (3.70%)  5/55 (9.09%) 
Psychiatric disorders     
ANXIETY  1  4/54 (7.41%)  5/55 (9.09%) 
DEPRESSION  1  3/54 (5.56%)  3/55 (5.45%) 
INSOMNIA  1  3/54 (5.56%)  2/55 (3.64%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  13/54 (24.07%)  10/55 (18.18%) 
DYSPNOEA  1  6/54 (11.11%)  12/55 (21.82%) 
EPISTAXIS  1  0/54 (0.00%)  3/55 (5.45%) 
OROPHARYNGEAL PAIN  1  2/54 (3.70%)  4/55 (7.27%) 
Skin and subcutaneous tissue disorders     
DRY SKIN  1  3/54 (5.56%)  0/55 (0.00%) 
ERYTHEMA  1  3/54 (5.56%)  1/55 (1.82%) 
PRURITUS  1  3/54 (5.56%)  3/55 (5.45%) 
PRURITUS GENERALISED  1  1/54 (1.85%)  3/55 (5.45%) 
RASH  1  9/54 (16.67%)  2/55 (3.64%) 
RASH MACULO-PAPULAR  1  3/54 (5.56%)  1/55 (1.82%) 
Vascular disorders     
HYPOTENSION  1  3/54 (5.56%)  3/55 (5.45%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
On 29 January 2013 the Stage 1 portion of the study was met and enrollment stopped. The Stage 1 results as assessed by the IRAC demonstrated that neither subtype met the prespecified requirement to be further studied in Stage 2.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain
Organization: Celgene
Phone: 1-888-260-1599
EMail: clinicaltrialdisclosure@celgene.com
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01197560     History of Changes
Other Study ID Numbers: CC-5013-DLC-001
First Submitted: July 29, 2010
First Posted: September 9, 2010
Results First Submitted: July 31, 2014
Results First Posted: August 20, 2014
Last Update Posted: April 17, 2019